Silicones are entirely synthetic polymers containing a repeating silicon-oxygen (Si--O) backbone with organic groups attached directly to the silicon atom through a carbon bond. The most common form of silicone is polydimethylsiloxane (PDMS) and has a repeating unit of (CH.sub.3).sub.2 SiO.
Silicone polymers have, until recently, been considered biologically and immunologically inert, and for this reason are included as exterior coatings or components of most medical devices that are surgically implanted into humans. Some examples of silicone-containing devices include hip replacements, catheters, mandibular prostheses, and breast implants. It is estimated that more than 2 million women in the United States have been recipients of silicone implants for augmentation mammoplasty and breast reconstruction following cancer surgery.
However, as devices such as silicone breast implants have become more widely used, there has arisen increased concern that silicone may be neither biologically nor immunologically inert. Silicone can be formed into fluids, gels or solids based on the degree of linear, branched, and cross-linked subunits. The degree of crosslinking dictates the consistency of the resulting silicone, which can vary from a clear gel to a white opaque elastomer. The crosslinked polymers form a loose intertwining matrix which retains the remaining silicone fluid. The lack of chemical integrity of this complex is suspected to permit "gel bleed" of silicone fluid slowly out of the matrix. Impurities such as catalyst, short linear polymers and small cyclics can remain depending on the stringency of the purification technique employed.
Approximately 10% of patients who receive medical devices containing silicone polymers experience complications including inflammation, severe muscle pain, or overt rheumatic (autoimmune) disease. Recently, silicone implants have been linked to multiple sclerosis-like symptoms, particularly in patients whose implants have ruptured. Yet, a portion of the approximately 2 million women in the United States who have received silicone gel filled breast implants have complications such as infection, capsular contraction, leakage, and rupture (Touchette, 1992). Additionally, some breast implant recipients experience a syndrome characterized by symptoms which include fibromyalgia, sicca syndrome, lymphadenopathy, contracture, sclerodactyly, alopecia, edema, telangiectasias, changes in pigmentation, recurrent fever, skin rash, and chronic fatigue (Brozena et al., 1988; Seleznick et al., 1991; Vasey et al., 1991; Copeland et al., 1993; Spiera and Kerr, 1993; Spiera et al., 1994). This syndrome, which also afflicts recipients of other silicone-containing medical devices, was previously termed human adjuvant disease (HAD) (Miyoshi et al., 1964; Miyoshi et al., 1973). Individuals surgically implanted with various devices containing silicone may also develop arthritic and dermatologic conditions that present autoimmune-like diseases, such as systemic sclerosis (scleroderma) or Sjogren's syndrome (Brozena et al., 1988; Vasey et al., 1991; Spiera et al., 1994). Studies implicating silicone-containing medical devices in autoimmune diseases, however, have been met with considerable skepticism (Gabriel et al., 1994).
Complications occurring after implantation of silicone-containing medical devices may generally fall in two categories:
1 ) Atypical Connective Tissue Disease (ACTD)/Atypical Rheumatic Syndrome(ARS)/Nonspecific Autoimmune Condition (NAC). Symptoms include tightness of skin, contracture, sclerodactyly, alopecia, oedema, telangiectasias, rash, and changes in pigmentation. These symptoms have been frequently associated with silicone breast implants, but occur also in recipients of other silicone-containing medical devices. PA1 2) Overt autoimmune diseases. Some investigators have reported that recipients of breast implants are more likely than non-implanted individuals to develop autoimmune diseases such as systemic lupus erythematosus or scleroderma. Increased levels of previously defined autoantibodies (SS-A, SS-B, Sm, etc.) have also been observed. PA1 (1) said patient has no polymeric implant, then the presence of said antibody indicates that the patient has a condition predisposing to SRD; PA1 (2) said patient has a polymeric implant, then the presence of said antibody indicates that the patient has SRD; PA1 (3) said patient has a polymeric implant, then the absence of said antibody indicates that the patient does not have SRD; PA1 (4) said patient has a polymeric implant and has been previously diagnosed as having undifferentiated rheumatoid disease selected from the group consisting of SRD, atypical connective tissue disease, atypical rheumatic syndrome, nonspecific autoimmune condition, or overt autoimmune diseases (such as CREST), then the presence of said antibody indicates said rheumatoid disease is SRD. PA1 (5) said patient has no polymeric implant and has previously been diagnosed as having an undifferentiated rheumatoid disease selected from the group consisting of SRD, atypical connective tissue disease, atypical rheumatic syndrome, nonspecific autoimmune condition, or overt autoimmune diseases (such as CREST), then the absence of said antibody indicates said rheumatoid disease is predisposing to SRD.
Exposure to silicone breast implants can result in the manifestation of symptoms and complications that collectively are dissimilar from previously recognized or defined rheumatological diseases, and therefore, may be uniquely identifiable with the appropriate diagnostic tests. Nevertheless, the systemic nature and relatively nonspecific symptoms of the diseases, particularly undifferentiated rheumatic diseases and SRD, often make the diseases difficult to diagnose and difficult to distinguish. An assay method which would enable the clinician to distinguish and discriminate between undifferentiated rheumatic diseases and SRD is highly desired.
Surgical implants have benefits that extend from prolongation of life to cosmetic enhancement. Implants also have associated risks, and these unknown risks motivate some people to forego implants, even though the benefit may outweigh the risk. Likewise, removal of existing implants may involve expense, pain, disfigurement, disability and death. A diagnostic test that would help an implant candidate balance the benefit and the risk of his/her implant is badly needed.